Polycystic Ovary Syndrome (PCOS) is a heterogeneous condition characterized by chronic anovulation and androgen excess that occurs in 4-8% of reproductive-aged women. The signs and symptoms of PCOS often are present at puberty although the diagnosis is often delayed until adulthood. Obesity is a common association with PCOS and is often present at an early age in these women. Insulin resitance is felt to play a critical pathophysiologic role in PCOS and interventions that have reduced insulin resistance have been shown to improve the metabolic and reproductive consequences of PCOS. The two most common interventions, weight reduction and use of insulin sensitizers, have not been evaluated in the long-term, and there are no controlled data on these interventions in the adolescent with PCOS. During the proposed K23 award, the PI will pursue research on the relative efficacy of pharmacologic and lifestyle interventions and test the overall hypothesis that these interventions to reduce insulin resistance in adult and adolescent women with PCOS will ameliorate their symptoms and improve metabolic parameters over the long-term. The significant public health impact of the metabolic and reproductive consequences of PCOS suggests the need for carefully done, controlled clinical trials of long-term intervention and follow-up. The PI will devote the next five years to developing a sound clincial trial program in PCOS, pursuing randomized, controlled pilot trials in the adult and adolescent with PCOS. The K23 award will allow the PI to gain the necessary background in epidemiology, clinical trial design and statistical analysis to propose and carry out a large-scale clinical trial assessing the relative benefits of insulin-sensitizing agents and lifestyle management. The perspective of both the adolescent with early onset of the disease, and the adult with more established morbidity, allows the exploration of these interventions across the reproductive life-span and provides a uinque opportunity to follow the long-term impact of treatment. [unreadable] [unreadable]